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Modelling the mechanobiological evolution of aneurysms : an integrative in vivo, in vitro and in silico approachMandaltsi, Aikaterini January 2016 (has links)
In silico models of intracranial aneurysm (IA) evolution aim to reliably represent the mechanical blood flow environment, the biology of the arterial wall and, crucially, the complex link between the two, namely the mechanobiology of healthy and diseased arteries. The ultimate goal is to create diagnostic tools for personalized management and treatment of aneurysm disease. Towards that target, the work presented in this thesis aims to establish a directly interactive link between experimental (in vivo and in vitro) and computational work for biologically and clinically relevant research on aneurysm disease. Mechanobiological hypotheses were firstly investigated in a novel 1D mathematical conceptual model of aneurysm evolution: for the first time these included representations of endothelial heterogeneity and smooth muscle cell (SMC) active stress response and apoptosis. The 1D investigations analysed and assessed the role of wall shear stress (WSS) homeostasis in elastin degradation, and the evolving role of the adventitia as a protective sheath in health and primary load-bearer in disease. The 1D framework was applied to a specific patient's aneurysm using both imaging and histological data to parameterise the model, calculating a material parameter for the adventitital collagen. The predicted evolution captured aspects of tissue changes measured with time focusing on the remodelled tissue wall thickness consistent with the experimental measurements, and physiological cyclic deformation in order to propose an approach to modelling adventitia's adaptive role to load bearing. Furthermore, an existing Fluid-Solid-Growth (FSG) computational framework was adapted and calibrated for the same patient-specific case with the help from the experimental data and the analysis from the 1D framework. This FSG model quantifies the arterial mechanical environment and captures the mechanical response of the fibrous arterial constituents. Comparing 1D and 3D investigations to establish consistency for our models, the 3Dmodel tested the hypothesis of WSS homeostasis, additionally introducing the element of spatial heterogeneity in the definition, and a new hypothesis linking cyclic deformation with collagen growth that ensures a physiological mechanical environment in stabilised aneurysms. Moreover, the FSG framework was applied in a specific rabbit aneurysm case and extended to link growth and remodeling to the detailed representation of the pulsatile blood flow mechanical environment. This research illustrates the power of computational modelling when coupled with rich data sets on the physiology, histology and geometry of healthy and diseased vascular tissue. In particular, the integrative modelling framework provides the foundation for establishing mechanobiological links crucial to aneurysm progression, and a basis for further research towards creating reliable aneurysm clinical tools.
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Modélisation numérique et expérimentale des interactions fluide structure en conduite sténosée : contribution à l'étude de la vulnérabilité de la plaque d'athérome carotidienne. / Numerical and experimental modeling of the fluid structure interaction in stenosed tube : contribution towards the analysis of carotid atheromatous plaque vulnerability.Belzacq, Tristan 19 March 2012 (has links)
La rupture de la plaque d'athérome carotidienne est la première cause des infarctus cérébraux. Pour prévenir ces accidents, l'endartérectomie carotidienne est le traitement le plus utilisé. La vulnérabilité de la plaque est en relation avec les efforts que le sang applique sur la plaque. Ces actions sont différentes suivant les propriétés constitutives, mécaniques et géométriques de la plaque. Plusieurs auteurs ont développé des modèles numériques de la plaque d'athérome carotidienne à partir desquels une analyse mécanique a permis de caractériser les déformations et les contraintes en lien avec la rupture de la plaque. Néanmoins, les caractéristiques d'une plaque vulnérable sont encore mal connues. Dans ce manuscrit, un modèle numérique de plaque d'athérome carotidienne est développé en interaction fluide-structure dans le but mieux comprendre comment les actions mécaniques du sang sur la plaque sont affectées par les propriétés mécaniques et géométriques de la plaque. Plusieurs résultats sont en concordance avec la littérature : la vulnérabilité de la plaque est associée à la sévérité de sténose et à l'épaisseur de la chape fibreuse. De plus une analyse de l'écoulement du sang, de la déformation de la plaque et des contraintes dans la plaque révèle que les effets de l'écoulement du sang sont amplifiés si la plaque est courte, si la pente en amont de sténose est raide ou si la morphologie de la plaque est irrégulière et asymétrique. Ces résultats offrent de nouvelles perspectives dans la compréhension de la vulnérabilité de la plaque. / The rupture of carotid atheromatous plaques is the major cause of cerebrovascular thromboembolic events such as strokes and ischemic attacks. To prevent this issue, carotid endarterectomy is the preferred treatment. The vulnerability of the plaque is related the mechanical action of the blood onto the plaque. This action is different according to the plaque morphology, the plaque constitution and the mechanical properties of the constituents. Several authors developed computational models to perform mechanical analyses for carotid atherosclerotic plaques and to identify critical mechanical descriptors as stresses or strains related to plaque rupture. But the question of which plaque characteristics affect the plaque rupture is not closely elucidated. In this manuscript a fluid structure interaction model is developed, questioning how the mechanical action of the blood onto an atheromatous plaque is affected by the mechanical and geometrical properties of the plaque. Many results are in agreement with the literature: the vulnerability of atheromatous plaques is related to the degree of severity of the endoluminal stenosis and the thickness of the fibrous cap. Moreover the resulting flow patterns, wall shear stresses, plaque deformations and stresses in the fibrous cap reveal that the effects of the blood flow are amplified if the plaque is short, if the slope upstream stenosis is steep or if the plaque morphology is irregular and asymmetric. These results offer new perspectives for understanding the vulnerability of plaques.
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Patient-Specific 3D Vascular Reconstruction and Computational Assessment of Biomechanics – an Application to Abdominal Aortic AneurysmRaut, Samarth Shankar 01 August 2012 (has links)
The current clinical management of abdominal aortic aneurysm (AAA) disease is based on measuring the aneurysm maximum diameter to decide when timely intervention can be recommended to a patient. However, other parameters may also play a role in causing or predisposing the AAA to either an early or delayed rupture relative to its size. Therefore, patient-specific assessment of rupture risk based on physical principles such as individualized biomechanics can be conducive to the development of a vascular tool with translational potential. To that end, the present doctoral research materialized into a framework for image based patient-specific vascular biomechanics assessment.
A robust generalized approach is described herein for image-based volume mesh generation of complex multidomain bifurcated vascular trees with the capability of incorporating regionally varying wall thickness. The developed framework is assessed for geometrical accuracy, mesh quality, and optimal computational performance. The relative influence of the shape and the constitutive wall material property on the AAA wall mechanics was explored. This study resulted in statistically insignificant differences in peak wall stress among 28 AAA geometries of similar maximum diameter (in the 50 – 55 mm range) when modeled with five different hyperelastic isotropic constitutive equations. Relative influence of regionally varying vs. uniform wall thickness distribution on the AAA wall mechanics was also assessed to find statistically significant differences in spatial maxima of wall stresses, strains, and strain energy densities among the same 28 AAA geometries modeled with patient-specific non-uniform wall thickness and two uniform wall thickness assumptions. Finally, the feasibility of estimating in vivo wall strains from individual clinical images was evaluated. Such study resulted in a framework for in vivo 3D strain distributions based on ECG gated, unenhanced, dynamic magnetic resonance images acquired for 20 phases in the cardiac cycle. Future efforts should be focused on further development of the framework for in vivo estimation of regionally varying hyperelastic, anisotropic constitutive material models with active mechanics components and the integration of such framework with an open source finite element solver with the goal of increasing the translational potential of these tools for individualized prediction of AAA rupture risk in the clinic.
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Biomechanical and morphological characterization of common iliac vein remodeling: Effects of venous reflux and hypertensionBrass, Margaret Mary January 2014 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / The passive properties of the venous wall are important in the development of venous pathology. Increase in venous pressure due to retrograde flow (reflux) and obstruction of venous flow by intrinsic and extrinsic means are the two possible mechanisms for venous hypertension. Reflux is the prevailing theory in the etiology of venous insufficiency. The objective of this thesis is to quantify the passive biomechanical response and structural remodeling of veins subjected to chronic venous reflux and hypertension. To investigate the effects of venous reflux on venous mechanics, the tricuspid valve was injured chronically in canines by disrupting the chordae tendineae. The conventional inflation-extension protocol in conjunction with intravascular ultrasound (IVUS) was utilized to investigate the passive biomechanical response of both control common iliac veins (from 9 dogs) and common iliac veins subjected to chronic venous reflux and hypertension (from 9 dogs). The change in thickness and constituent composition as a result of chronic venous reflux and hypertension was quantified using multiphoton microscopy (MPM) and histological evaluation. Biomechanical results indicate that the veins stiffened and became less compliant when exposed to eight weeks of chronic venous reflux and hypertension. The mechanical stiffening was found to be a result of a significant increase in wall thickness (p < 0.05) and a significant increase in the collagen to elastin ratio (p < 0.05). After eight weeks of chronic reflux, the circumferential Cauchy stress significantly reduced (p < 0.05) due to wall thickening, but was not restored to control levels. This provided a useful model for development and further analysis of chronic venous insufficiency and assessment of possible intervention strategies.
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